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Cognitive dysfunction in young subjects with periodontal disease

Hategan, Simona I; Kamer, Sabrina A; Craig, Ronald G; Sinescu, Cosmin; de Leon, Mony J; Jianu, Dragos C; Marian, Catalin; Bora, Bianca I; Dan, Traian-Flavius; Birdac, Claudiu D; Marcu, Anca; Kamer, Angela R; Negrutiu, Meda Lavinia
BACKGROUND:Periodontal disease is an inflammatory, dysbiotic condition. Studies have shown that in the elderly, periodontal disease was associated with cognitive dysfunction and Alzheimer's disease. OBJECTIVE:To investigate whether young healthy subjects with periodontal disease have lower cognition compared to those without periodontal disease. The salivary cytokines (IL-1β, TNF-α) levels in relation to cognition were also tested. METHODS:In a monocenter, cross-sectional study, forty subjects [mean age (SD) = 34 (5) and 48% female] from western Romania were classified into periodontal disease conditions using radiographic assessment: 10 subjects had aggressive periodontitis (AGG_P), 20 chronic mild-moderate periodontitis (CR_P), and 10 no periodontitis (NL_P). Neuropsychological assessment performed by standardized neurologists and psychologist included Rey Auditory Verbal Learning Test (RAVLT), Montreal Cognitive Assessment test (MOCA), Mini-Mental State Examination (MMSE), and Prague tests. Salivary cytokines levels were determined by ELISA. RESULTS:RAVLT and MOCA delayed recall scores were lower in AGG_P group compared to NL_P and CR_P. The learning curve was also different with subjects with AGG_P showing reduced learning performance. Contrary to our hypothesis, salivary IL-1β associated with immediate but not delayed cognitive scores. CONCLUSIONS:These results showed for the first time that subjects with AGG_P had cognitive dysfunction and IL-1β may play a role in this process.
PMID: 33606127
ISSN: 1590-3478
CID: 4819332

Periodontal dysbiosis associates with reduced CSF Aβ42 in cognitively normal elderly

Kamer, Angela R; Pushalkar, Smruti; Gulivindala, Deepthi; Butler, Tracy; Li, Yi; Annam, Kumar Raghava Chowdary; Glodzik, Lidia; Ballman, Karla V; Corby, Patricia M; Blennow, Kaj; Zetterberg, Henrik; Saxena, Deepak; de Leon, Mony J
Introduction/UNASSIGNED:Periodontal disease is a chronic, inflammatory bacterial dysbiosis that is associated with both Alzheimer's disease (AD) and Down syndrome. Methods/UNASSIGNED:A total of 48 elderly cognitively normal subjects were evaluated for differences in subgingival periodontal bacteria (assayed by 16S rRNA sequencing) between cerebrospinal fluid (CSF) biomarker groups of amyloid and neurofibrillary pathology. A dysbiotic index (DI) was defined at the genus level as the abundance ratio of known periodontal bacteria to healthy bacteria. Analysis of variance/analysis of covariance (ANOVA/ANCOVA), linear discriminant effect-size analyses (LEfSe) were used to determine the bacterial genera and species differences between the CSF biomarker groups. Results/UNASSIGNED: = 0.02 and 0.01) but not with P-tau. Discussion/UNASSIGNED:We show a selective relationship between periodontal disease bacterial dysbiosis and CSF biomarkers of amyloidosis, but not for tau. Further modeling is needed to establish the direct link between oral bacteria and Aβ.
PMID: 33869725
ISSN: 2352-8729
CID: 4894752

Current Considerations for Clinical Management and Care of People with HIV: Findings from the 11th Annual International HIV and Aging Workshop

Kamkwalala, Asante R.; Garg, Ankita; Roy, Upal; Matthews, Avery; Castillo-Mancilla, Jose; Lake, Jordan E.; Sebastiani, Giada; Yin, Michael; Brown, Todd T.; Kamer, Angela R.; Jabs, Douglas A.; Ellis, Ronald J.; Boffito, Marta; Greene, Meredith; Schmalzle, Sarah; Siegler, Eugenia; Erlandson, Kristine M.; Moore, David J.
ISSN: 0889-2229
CID: 5017662

The Influences of Bioinformatics Tools and Reference Databases in Analyzing the Human Oral Microbial Community

Sierra, Maria A; Li, Qianhao; Pushalkar, Smruti; Paul, Bidisha; Sandoval, Tito A; Kamer, Angela R; Corby, Patricia; Guo, Yuqi; Ruff, Ryan Richard; Alekseyenko, Alexander V; Li, Xin; Saxena, Deepak
There is currently no criterion to select appropriate bioinformatics tools and reference databases for analysis of 16S rRNA amplicon data in the human oral microbiome. Our study aims to determine the influence of multiple tools and reference databases on α-diversity measurements and β-diversity comparisons analyzing the human oral microbiome. We compared the results of taxonomical classification by Greengenes, the Human Oral Microbiome Database (HOMD), National Center for Biotechnology Information (NCBI) 16S, SILVA, and the Ribosomal Database Project (RDP) using Quantitative Insights Into Microbial Ecology (QIIME) and the Divisive Amplicon Denoising Algorithm (DADA2). There were 15 phyla present in all of the analyses, four phyla exclusive to certain databases, and different numbers of genera were identified in each database. Common genera found in the oral microbiome, such as Veillonella, Rothia, and Prevotella, are annotated by all databases; however, less common genera, such as Bulleidia and Paludibacter, are only annotated by large databases, such as Greengenes. Our results indicate that using different reference databases in 16S rRNA amplicon data analysis could lead to different taxonomic compositions, especially at genus level. There are a variety of databases available, but there are no defined criteria for data curation and validation of annotations, which can affect the accuracy and reproducibility of results, making it difficult to compare data across studies.
PMID: 32756341
ISSN: 2073-4425
CID: 4554112

Periodontal disease as a possible cause for Alzheimer's disease

Kamer, Angela R; Craig, Ronald G; Niederman, Richard; Fortea, Juan; de Leon, Mony J
Approximately 47 million people worldwide have been diagnosed with dementia, 60%-80% of whom have dementia of the Alzheimer's disease type. Unfortunately, there is no cure in sight. Defining modifiable risk factors for Alzheimer's disease may have a significant impact on its prevalence. An increasing body of evidence suggests that chronic inflammation and microbial dysbiosis are risk factors for Alzheimer's disease. Periodontal disease is a chronic inflammatory disease that develops in response to response to microbial dysbiosis. Many studies have shown an association between periodontal disease and Alzheimer's disease. The intent of this paper was to review the existing literature and determine, using the Bradford Hill criteria, whether periodontal disease is causally related to Alzheimer's disease.
PMID: 32385876
ISSN: 1600-0757
CID: 4430702

Electronic Cigarette Aerosol Modulates the Oral Microbiome and Increases Risk of Infection

Pushalkar, Smruti; Paul, Bidisha; Li, Qianhao; Yang, Jian; Vasconcelos, Rebeca; Makwana, Shreya; González, Juan Muñoz; Shah, Shivm; Xie, Chengzhi; Janal, Malvin N; Queiroz, Erica; Bederoff, Maria; Leinwand, Joshua; Solarewicz, Julia; Xu, Fangxi; Aboseria, Eman; Guo, Yuqi; Aguallo, Deanna; Gomez, Claudia; Kamer, Angela; Shelley, Donna; Aphinyanaphongs, Yindalon; Barber, Cheryl; Gordon, Terry; Corby, Patricia; Li, Xin; Saxena, Deepak
The trend of e-cigarette use among teens is ever increasing. Here we show the dysbiotic oral microbial ecology in e-cigarette users influencing the local host immune environment compared with non-smoker controls and cigarette smokers. Using 16S rRNA high-throughput sequencing, we evaluated 119 human participants, 40 in each of the three cohorts, and found significantly altered beta-diversity in e-cigarette users (p = 0.006) when compared with never smokers or tobacco cigarette smokers. The abundance of Porphyromonas and Veillonella (p = 0.008) was higher among vapers. Interleukin (IL)-6 and IL-1β were highly elevated in e-cigarette users when compared with non-users. Epithelial cell-exposed e-cigarette aerosols were more susceptible for infection. In vitro infection model of premalignant Leuk-1 and malignant cell lines exposed to e-cigarette aerosol and challenged by Porphyromonas gingivalis and Fusobacterium nucleatum resulted in elevated inflammatory response. Our findings for the first time demonstrate that e-cigarette users are more prone to infection.
PMID: 32105635
ISSN: 2589-0042
CID: 4323572

Microbes and Alzheimer's Disease

Itzhaki, Ruth F; Lathe, Richard; Balin, Brian J; Ball, Melvyn J; Bearer, Elaine L; Braak, Heiko; Bullido, Maria J; Carter, Chris; Clerici, Mario; Cosby, S Louise; Del Tredici, Kelly; Field, Hugh; Fulop, Tamas; Grassi, Claudio; Griffin, W Sue T; Haas, Jurgen; Hudson, Alan P; Kamer, Angela R; Kell, Douglas B; Licastro, Federico; Letenneur, Luc; Lovheim, Hugo; Mancuso, Roberta; Miklossy, Judith; Lagunas, Carola Otth; Palamara, Anna Teresa; Perry, George; Preston, Christopher; Pretorius, Etheresia; Strandberg, Timo; Tabet, Naji; Taylor-Robinson, Simon D; Whittum-Hudson, Judith A
PMID: 26967229
ISSN: 1875-8908
CID: 2024652

Effects of vascular risk factors, statins, and antihypertensive drugs on PiB deposition in cognitively normal subjects

Glodzik, Lidia; Rusinek, Henry; Kamer, Angela; Pirraglia, Elizabeth; Tsui, Wai; Mosconi, Lisa; Li, Yi; McHugh, Pauline; Murray, John; Williams, Schantel; Osorio, Ricardo S; Randall, Catherine; Butler, Tracy; Deshpande, Anup; Vallabhajolusa, Shankar; de Leon, Mony
INTRODUCTION: Hypertension, hypercholesterolemia, and obesity increase the risk of dementia. Although their detection is commonly followed by an introduction of treatment, little is known about how medications frequently used to treat vascular risk affect amyloid deposition. METHODS: A cross-sectional study of 156 subjects who underwent positron emission tomography with PiB. Using linear regression, we tested whether blood pressure, cholesterol, overweight/obese status, angiotensin receptor blockers (ARBs), beta-blockers, diuretics, angiotensin converting enzyme inhibitors, and statins predicted amyloid deposition. RESULTS: The use of ARBs (beta = -.15, P = .044) and diuretics (beta = -.20, P = .006) predicted less amyloid accumulation; older age (beta = .29, P < .001) and statins (beta = .23, P = .004) were related to greater amyloid deposition. Overweight and/or obese women had more cortical amyloid than their peers. DISCUSSION: Prospective studies should confirm effects of drugs and increased body weight on amyloid accumulation and establish whether they translate into measurable clinical outcomes. Women may be more susceptible to harmful effects of obesity.
PMID: 27239540
ISSN: 2352-8729
CID: 2120682

Periodontal disease's contribution to Alzheimer's disease progression in Down syndrome

Kamer, Angela R; Fortea, Juan O; Videla, Sebastia; Mayoral, Angela; Janal, Malvin; Carmona-Iragui, Maria; Benejam, Bessy; Craig, Ronald G; Saxena, Deepak; Corby, Patricia; Glodzik, Lidia; Annam, Kumar Raghava Chowdary; Robbins, Miriam; de Leon, Mony J
People with Down syndrome (DS) are at an increased risk for Alzheimer's disease (AD). After 60 years of age, >50% of DS subjects acquire dementia. Nevertheless, the age of onset is highly variable possibly because of both genetic and environmental factors. Genetics cannot be modified, but environmental risk factors present a potentially relevant intervention for DS persons at risk for AD. Among them, inflammation, important in AD of DS type, is potential target. Consistent with this hypothesis, chronic peripheral inflammation and infections may contribute to AD pathogenesis in DS. People with DS have an aggressive form of periodontitis characterized by rapid progression, significant bacterial and inflammatory burden, and an onset as early as 6 years of age. This review offers a hypothetical mechanistic link between periodontitis and AD in the DS population. Because periodontitis is a treatable condition, it may be a readily modifiable risk factor for AD.
PMID: 27239536
ISSN: 2352-8729
CID: 2124952

Letter to the editor regarding: Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective [Letter]

Kamer, Angela R; Janal, Malvin N; de Leon, Mony
PMID: 27239519
ISSN: 2352-8729
CID: 2124732